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Unformatted text preview: Selection-Driven Evolution of Emergent Dengue Virus Shannon N. Bennett,* Edward C. Holmes, Maritza Chirivella, à § Dania M. Rodriguez,* Manuela Beltran, § Vance Vorndam, § Duane J. Gubler, k and W. Owen McMillan* *Department of Biology, University of Puerto Rico–Rio Piedras, San Juan, Puerto Rico; Department of Zoology, University of Oxford, Oxford, England; à Department of Microbiology and Medical Zoology, University of Puerto Rico–Ciencias Medicas, San Juan, Puerto Rico; §Centers for Disease Control and Prevention, San Juan Branch, San Juan, Puerto Rico; k Centers for Disease Control and Prevention, Fort Collins, Colorado In the last four decades the incidence of dengue fever has increased 30-fold worldwide, and over half the world’s population is now threatened with infection from one or more of four co-circulating viral serotypes (DEN-1 through DEN-4). To determine the role of viral molecular evolution in emergent disease dynamics, we sequenced 40% of the genome of 82 DEN-4 isolates collected from Puerto Rico over the 20 years since the onset of endemic dengue on the island. Isolates were derived from years with varying levels of DEN-4 prevalence. Over our sampling period there were marked evolutionary shifts in DEN-4 viral populations circulating in Puerto Rico; viral lineages were temporally clustered and the most common genotype at a particular sampling time often arose from a previously rare lineage. Expressed changes in structural genes did not appear to drive this lineage turnover, even though these regions include primary determinants of viral antigenic properties. Instead, recent dengue evolution can be attributed in part to positive selection on the nonstructural gene 2A ( NS2A ), whose functions may include replication efficiency and antigenicity. During the latest and most severe DEN-4 epidemic in Puerto Rico, in 1998, viruses were distinguished by three amino acid changes in NS2A that were fixed far faster than expected by drift alone. Our study therefore demonstrates viral genetic turnover within a focal population and the potential importance of adaptive evolution in viral epidemic expansion. Introduction RNA viruses comprise one of the fastest growing categories of emergent diseases (Domingo and Holland 1997). Although they exhibit remarkable genetic diversity, attributable to intrinsically high rates of mutation and replication as well as large population sizes (Domingo and Holland 1997; Drake and Holland 1999), the role of viral evolution in determining disease dynamics has only been described in a few cases (for example, Bush et al. 1999; Zanotto et al. 1999; Manzin et al. 2000; Hatta et al. 2001). We examine evolutionary change in dengue (DEN), an acute mosquito-borne RNA virus (genus Flavivirus ), over a 20-year period that has marked the emergence of dengue in Puerto Rico (PR), a dense urban population whose growth rate rivals Asian population centers. The virus, which causes dengue fever (DF), and the more severe...
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This note was uploaded on 07/12/2011 for the course BIO 620 taught by Professor Hardy during the Spring '11 term at University of Florida.
- Spring '11